We tested the hypothesis that lymphocytes from swine with susceptibility to malignant hyperthermia (MH) had calcium extrusion activity higher than unaffected swine. Cytoplasmic concentration of ionized calcium was determined by use of dual emission spectrofluorometry and measurement of the ratio of free to calcium-bound form of the fluorescent calcium dye indo-1. Net calcium accumulation and unidirectional calcium extrusion rate were dependent on intracellular calcium concentration. Calcium extrusion from calcium-loaded lymphocytes was monitored while calcium influx was inhibited by suspending the cells in calcium-free medium with a calcium chelator. Net calcium accumulation of untreated lymphocytes was monitored in calcium-replete medium. A novel method of calculation of ionized calcium was used. This method confirmed our previous findings of lower ionized calcium concentration (86 +/- 40 and 370 +/- 216 nmol/L; P < 0.01) and slower rates of calcium accumulation (39 +/- 16 and 127 +/- 52 nmol/L/min) in untreated lymphocytes from MH-susceptible swine compared with controls. These changes were attributable to calcium extrusion activity two- to three-fold higher in lymphocytes of MH-susceptible swine (154 +/- 36 and 408 +/- 47 nmol/L/min at 175 nmol/L; 972 +/- 111 and 1,690 +/- 505 nmol/L/min at 425 nmol/L). These data were compatible with our model of higher calcium extrusion activity being a compensatory adaptation of MH-susceptible swine lymphocytes to their hypersensitivity to stimuli that increase cytoplasmic calcium concentration.

Programmed electrical stimulation techniques were used to evaluate the effects of halothane and isoflurane on induction of atrial fibrillation in anesthetized dogs. Experiments were performed in 16 dogs anesthetized with alpha-chloralose. Critically timed premature stimuli were applied to the right atrial appendage and Bachmann bundle to determine the atrial fibrillation threshold, defined as the minimal current required to induce rapid, irregular atrial electrical activity of at least 8 seconds' duration. Atrial fibrillation thresholds were determined at baseline (0.0% inhalational anesthetic), 0.5 minimal alveolar concentration (MAC), and 1.0 MAC of halothane (n = 8) and isoflurane (n = 8). In the absence of inhalation anesthetic, it was significantly (P < 0.01) easier to induce atrial fibrillation at the Bachmann bundle vs the right atrial appendage. Atrial fibrillation threshold at the Bachmann bundle was not affected by increasing concentrations of halothane, but was increased by 1.0 MAC of isoflurane (P < 0.05). It was concluded that at 1.0 MAC isoflurane, but not halothane, has antifibrillatory effects in atrial tissue.

Cardiovascular effects of butorphanol (0.2 mg/kg of body weight, IV) and responses associated with subsequent administration of naloxone (0.04 mg/kg, IV) were studied in halothane (1.2% end-tidal concentration)-anesthetized dogs. Transient, but statistically significant (P < 0.05), decreases in heart rate, mean and diastolic arterial blood pressures, and rate-pressure product were observed after butorphanol administration. Cardiac index, stroke volume, and systemic vascular resistance did not change significantly. Except for the decrease in heart rate, changes in the values of the cardiovascular variables measured after butorphanol administration did not appear to be clinically relevant. Sixty minutes after butorphanol administration, naloxone was given. Statistically significant (P < 0.05) increases in heart rate, arterial blood pressures, cardiac index, and rate-pressure product, along with dysrhythmias were observed. Stroke volume and systemic vascular resistance remained unchanged after administration of naloxone. Naloxone administration was associated with changes indicative of increased myocardial oxygen consumption.

A controlled study of the cardiovascular responses in horses anesthetized with acepromazine (0.05 mg/kg of body weight, IV), guaifenesin (100 mg/kg, IV), thiamylal (5.0 mg/kg, IV), and halothane in O2 (1.2 to 1.4% end-expired concentration) was performed to determine whether hypotension could be prevented by use of various treatments. Six horses were given 5 treatments in a randomized sequence: no treatment (control), methoxamine (0.04 mg/kg IV), lactated Ringer solution (20.0 ml/kg, IV), 7.5% hypertonic saline solution (4.0 ml/kg, IV), or constant infusion of dobutamine (5.0 mg/kg/min, IV) during anesthesia. Heart rate, ECG, blood pressure, central venous pressure, cardiac output, blood gas analysis, PCV, and plasma total protein concentration were measured during the study. Compared with the control value, an increase in blood pressure during halothane administration was observed after administration of lactated Ringer solution, hypertonic saline solution, or dobutamine (P < 0.05). The improved blood pressure response to hypertonic saline solution and dobutamine was related to an increase in cardiac output, which was statistically significant (P < 0.05) Other statistically significant differences in cardiopulmonary responses among treatments were not observed during anesthesia. The PCV was increased in response to dobutamine infusion, and plasma total protein concentration was reduced in response to administration of hypertonic saline or lactated Ringer solution.

The ventricular arrhythmogenic dose of epinephrine (ADE) was determined in 6 dogs anesthetized with halothane alone or with halothane after injection of tiletamine/zolazepam (TZ). Respiratory rate and tidal volume were controlled and sodium bicarbonate was administered to maintain arterial pH and blood gas values within reference range. Heart rate and arterial blood pressure were recorded during determination of the ADE. The ADE (mean +/- SD) was no different during anesthesia with use of halothane alone (8.9 +/- 4.3) than it was when injections of TZ preceded administration of halothane (6.7 +/- 2.8). Tiletamine/zolazepam was also administered IV immediately after determination of the ADE during halothane-induced anesthesia. The TZ administered in this manner did not alter the ADE. Blood pressure and heart rate were significantly greater during infusion of epinephrine than immediately prior to infusion. The administration of TZ did not alter blood pressure response. The ADE was also determined in 6 cats anesthetized with halothane preceded by administration of TZ. The ADE (mean +/- SD) was 0.7 +/- 0.23 microgram/kg, a value similar to that reported for cats during anesthesia with halothane alone.

The carotid artery of clinically normal goats was examined, using duplex ultrasonography and arteriography. The diameter of the carotid artery was measured by use of two-dimensional ultrasonography and Doppler ultrasonography, respectively, before and after xylazine administration. The diameter of the artery was also measured by use of an arteriography technique in halothane-anesthetized goats. There was no significant difference between the mean diameter of the carotid artery measured by ultrasonography in conscious nonsedated goats and that determined by arteriography in goats under halothane anesthesia. On the other hand, ultrasonography of xylazine-sedated goats revealed an increase of carotid artery diameter of 20 to 30%. There was no change in the velocity of blood flow after xylazine administration.

Cardiovascular and respiratory functions were serially characterized in 7 healthy, spontaneously breathing, adult horses (from which food had been withheld) during 5 hours of constant 1.06% alveolar halothane (end-expired halothane concentration of 1.06%; equivalent to 1.2 times the minimal alveolar anesthetic concentration for horses). To enable comparison of temporal results in relation to 2 body postures, horses were studied in lateral recumbency (LR) and dorsal recumbency (DR) on separate occasions. Temporal changes in results of measures of circulation previously reported from this laboratory for horses in LR were confirmed (ie, a time-related increase in systemic arterial blood pressure, cardiac output, stroke volume, and PCV). During DR, systemic arterial blood pressure was initially significantly (P < 0.05) greater and pulmonary artery pressure less than results at comparable periods during LR. Differences ceased to exist with duration of anesthesia. Except for a greater heart rate at hour 5 of DR, no other significant differences in circulation were found between LR and DR. In general, except for PaO2, measures of ventilation did not change with time in either LR or DR. The PaO2 was significantly greater during LR, compared with DR, but the average did not change significantly with time in either body posture.

Anesthesia of equids is associated with pulmonary dysfunction. Cardiovascular and respiratory effects of inhalation anesthetic agents and duration of anesthesia have been studied, using oxygen as the carrier gas. To our knowledge, the effects of inspired oxygen have not been determined. We studied the cardiovascular and respiratory effects of 2 inspired oxygen fractions (0.30 and > 0.85) in 5 laterally recumbent, halothane-anesthetized horses. Mean systemic arterial blood pressure, cardiac output, central venous pressure, pulmonary arterial pressure, arterial pH, and arterial base excess were similar in horses of the 2 groups during 4 hours of anesthesia at constant end-tidal halothane concentration. End-tidal partial pressure of CO2, arterial partial pressure of CO2 and O2, and alveolar-to-arterial O2 tension difference were greater in horses exposed to the higher oxygen concentration. On the basis of the data obtained, we suggest that greater hypoventilation and ventilation/perfusion mismatch occur when horses are breathing high-oxygen fraction. Arterial partial pressure of O2 was not different between the 2 groups of horses after they were disconnected from the anesthesia circuit and allowed to breathe room air. Horses recovered from anesthesia without complications.

The relative myocardial irritant properties of halothane, isoflurane, and pentobarbital were evaluated in chickens. Sixteen adult male broiler chickens were randomly assigned to 1 of 3 groups: group-1 chickens were anesthetized with pentobarbital (30 mg/kg, IV), group-2 chickens were anesthetized with halothane (end tidal halothane 1.2%), and group-3 chickens were anesthetized with isoflurane (end tidal isoflurane 2.1%). Birds in any 2 of the 3 treatment groups were tested on any 1 day. Local anesthesia was induced, and blood pressure, heart rate, ECG, and blood gas variables were measured before general anesthesia was induced. Positive-pressure ventilation with an inspired O2 fraction > 0.95 was adjusted to result in an end tidal CO2 concentration that reflected a PaCO2 similar to that obtained prior to anesthesia and ventilation. All measurements were repeated. The threshold for ventricular fibrillation in response to electrical stimulation of the heart was then determined for all birds. Effects of anesthesia on hemodynamic and blood gas variables were similar in all 3 groups. Compared with halothane or pentobarbital, isoflurane anesthesia resulted in a significantly (P < 0.05) lower threshold for electrical fibrillation of the heart.

The effects of different arterial carbon dioxide tensions (PaCO2) on cerebrospinal fluid pressure (CSFP) and intraocular pressure (IOP) were studied in 6 male halothaneanesthetized horses positioned in left lateral recumbency. Steady-state anesthetic conditions (1.06% end-tidal halothane concentration) commenced 60 minutes following anesthetic induction with only halothane in oxygen. During atracurium neuromuscular blockade, horses were ventilated, and respiratory rate and peak inspiratory airway pressure were maintained within narrow limits. The CSFP and IOP were measured at 3 different levels of PaCO2 (approx 40, 60, and 80 mm of Hg). The PaCO2 sequence in each horse was determined from a type of switchback design with the initial PaCO2 (period 1), established 30 minutes after the commencement of steady-state anesthesia, being repeated in the middle (period 3) and again at the end (period 5) of the experiment. Measurements taken from the middle 3 periods (2, 3, and 4) would form a Latin square design replicated twice. The interval between each period was approximately 45 minutes. Data from periods 2, 3, and 4 indicated that CSFP (P < 0.05) and mean systemic arterial pressure increased significantly (P < 0.05) with high PaCO2. Mean central venous pressure, heart rate, and IOP did not change significantly during these same conditions. Measurements taken during periods 1, 3, and 5 were compared to assess the time-related responses to anesthesia and showed a significant increase in CSFP, a significant decrease in mean central venous pressure, and a small (but not statistically significant) increase in mean systemic arterial pressure.